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Open AccessArticle

Evidence for Involvement of IL-9 and IL-22 in Cows’ Milk Allergy in Infants

Department of Physiology, Federal University of São Paulo, São Paulo SP CEP 04023-900, Brazil
Department of Biological Sciences, Federal University of São Paulo, Diadema SP CEP 09972-270, Brazil
Department of Pediatrics, Faculty of Medicine, Federal University of ABC, Santo André SP CEP 09210-580, Brazil
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK
National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton SO16 6YD, UK
Author to whom correspondence should be addressed.
Nutrients 2017, 9(10), 1048;
Received: 2 August 2017 / Revised: 7 September 2017 / Accepted: 18 September 2017 / Published: 21 September 2017
Although allergic inflammation is characterized by a T helper (Th) 2-dominant immune response, the discovery of a role for new T cell subsets in inflammatory diseases has added an additional layer of complexity to the understanding of the pathogeneses of allergic diseases. We evaluated plasma cytokine profiles in infants with cows’ milk allergy (CMA), who were being treated with an elimination diet. In a prospective, randomized and controlled study, infants (aged 8.4 ± 3.9 months) with CMA were treated with an elimination diet for 120 days, which replaced cows’ milk with a hydrolysed soy protein formula (n = 26) or a free amino acid formula (n = 20). Blood samples were collected before treatment during active disease (T0) and after 120 days, when symptoms were absent (T1). Plasma cytokine concentrations were measured. Infants with CMA had higher plasma concentrations of interleukin (IL)-4 and IL-13 and lower concentrations of IL-9, IL-17A and interferon-γ, compared with healthy breast-fed infants. At T0, there was a positive correlation between blood eosinophil numbers and plasma concentrations of IL-4, IL-9, IL-17A and IL-22. Treatment with a cows’ milk elimination diet resulted in a decrease in plasma IL-4, IL-9, IL-13 and IL-22 and an increase in plasma IL-17A. We conclude that IL-4 and IL-13 are elevated in active CMA. The association of IL-9 and IL-22 with eosinophilia, and the decrease in these two cytokines with cows’ milk elimination, suggests that they both play a role in the symptoms observed in CMA and may be important targets for future interventions. View Full-Text
Keywords: cows’ milk allergy; cytokine; dietetic treatment; hydrolysed soy formula; free amino acid formula cows’ milk allergy; cytokine; dietetic treatment; hydrolysed soy formula; free amino acid formula
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Barros, K.V.; Flor Silveira, V.L.; Laranjeira, M.S.; Wandalsen, N.F.; Passeti, S.; De Oliveira, R.; Munekata, R.V.; Noakes, P.S.; Miles, E.A.; Calder, P.C. Evidence for Involvement of IL-9 and IL-22 in Cows’ Milk Allergy in Infants. Nutrients 2017, 9, 1048.

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